Genome-wide Nucleosome Specificity and Directionality of Chromatin Remodelers

Yen, Kuangyu; Vinayachandran, Vinesh; Batta, Kiran; Koerber, R. Thomas; Pugh, B. Franklin

doi:10.1016/j.cell.2012.04.036

Cited by 320 publications

(415 citation statements)

References 67 publications

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“…Our findings identify the Ies2 protein as a potent activator of Ino80 catalytic activity and bring to light an important role for the Ies6 and Arp5 proteins in nucleosome recognition and binding. These observations may provide a mechanistic basis for previous evidence that Ies2, Arp5, and Ies6 contribute to various Ino80-dependent nuclear transactions in fungi and in higher eukaryotes (4,10,(22)(23)(24)(25).…”

Section: Insertion Region Of the Ino80 Snf2-like Atpase Domain Directsmentioning

confidence: 65%

Multiple modes of regulation of the human Ino80 SNF2 ATPase by subunits of the INO80 chromatin-remodeling complex

Chen

Conaway

2013

Proc. Natl. Acad. Sci. U.S.A.

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SNF2 family ATPases are ATP-dependent motors that often function in multisubunit complexes to regulate chromatin structure. Although the central role of SNF2 ATPases in chromatin biology is well established, mechanisms by which their catalytic activities are regulated by additional subunits of chromatin-remodeling complexes are less well understood. Here we present evidence that the human Inositol auxotrophy 80 (Ino80) SNF2 ATPase is subject to regulation at multiple levels in the INO80 chromatin-remodeling complex. The zinc finger histidine triad domain-containing protein Ies2 (Ino Eighty Subunit 2) functions as a potent activator of the intrinsic catalytic activity of the Ino80 ATPase, whereas the YL-1 family Ies6 (Ino Eighty Subunit 6) and actin-related Arp5 proteins function together to promote binding of the Ino80 ATPase to nucleosomes. These findings support the idea that both substrate recognition and the intrinsic catalytic activities of SNF2 ATPases have evolved as important sites for their regulation. Although it is well established that SNF2 family ATPases have evolved to play critical roles as ATPdependent motors that drive many types of chromatin transactions, in most cases how their intrinsic catalytic activities are regulated by their diverse array of associated proteins is poorly understood.The INO80 complex was first identified in Saccharomyces cerevisiae, where it was shown to be composed of roughly 15 subunits (1, 9). Subsequent purification of the human INO80 complex revealed that it shares with its S. cerevisiae counterpart a set of subunits including the Ino80 SNF2 ATPase, the AAA+ ATPases Tip49a and Tip49b, actin-related proteins Arp4, Arp5, and Arp8, and the Ies2 and Ies6 proteins (2, 10-12). The human INO80 complex lacks orthologs of the remaining subunits of the S. cerevisiae INO80 complex and contains instead several apparently metazoan-specific subunits including the deubiquitinating enzyme Uch37, the gene altered in glioma (GLI)-Kruppel family zinc finger transcription factor YY1, the forkhead-associated domain (FHA) containing Mcrs1, nuclear factor related to kB (Nfrkb), and the Amida, Ino80D (FLJ20309), and Ino80E (FLJ90652) proteins.The INO80 complex is capable of regulating chromatin structure in at least two ways. First, it catalyzes ATP-dependent sliding of histone octamers along DNA (1, 2). Second, it catalyzes the replacement of histone H2AZ/histone H2AB dimers in nucleosomes with histone H2A/histone H2B dimers in a reaction that in yeast has been shown to contribute to genome-wide histone H2AZ localization (13).In a recent study dissecting mechanism(s) by which the human INO80 complex catalyzes chromatin remodeling, we found that it is composed of at least three modules that assemble with three distinct domains of the Ino80 protein (14) (Fig. 1A). One module is composed of an Ino80 N-terminal domain and all of the metazoan-specific subunits except YY1. A second, the helicase-SANT-associated (HSA) module, is composed of the Ino80 HSA domain, the actin-related Arp4/Baf53a and ...

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Section: Insertion Region Of the Ino80 Snf2-like Atpase Domain Directsmentioning

confidence: 65%

Multiple modes of regulation of the human Ino80 SNF2 ATPase by subunits of the INO80 chromatin-remodeling complex

Chen

Conaway

2013

Proc. Natl. Acad. Sci. U.S.A.

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“…After blotting to 0.2‐micron nitrocellulose membrane blotted bands were immunodetected with Nap1 and TBP (TATA binding protein) antibodies. For micrococcal nuclease (MNase) digestion (Yen et al , 2012), the chromatin pellets were washed with NPS buffer (50 mM NaCl, 10 mM Tris, pH 7.5, 5 mM MgCl 2 , 1 mM CaCl 2 ). For MNase‐seq (Fig 1), NPS also contained 0.5 mM spermidine, 0.075% IGEPAL.…”

Section: Methodsmentioning

confidence: 99%

Structural evidence for Nap1‐dependent H2A–H2B deposition and nucleosome assembly

et al. 2016

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Nap1 is a histone chaperone involved in the nuclear import of H2A–H2B and nucleosome assembly. Here, we report the crystal structure of Nap1 bound to H2A–H2B together with in vitro and in vivo functional studies that elucidate the principles underlying Nap1‐mediated H2A–H2B chaperoning and nucleosome assembly. A Nap1 dimer provides an acidic binding surface and asymmetrically engages a single H2A–H2B heterodimer. Oligomerization of the Nap1–H2A–H2B complex results in burial of surfaces required for deposition of H2A–H2B into nucleosomes. Chromatin immunoprecipitation‐exonuclease (ChIP‐exo) analysis shows that Nap1 is required for H2A–H2B deposition across the genome. Mutants that interfere with Nap1 oligomerization exhibit severe nucleosome assembly defects showing that oligomerization is essential for the chaperone function. These findings establish the molecular basis for Nap1‐mediated H2A–H2B deposition and nucleosome assembly.

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“…To determine the relative contribution of each histone PTM in targeting the NuA3 complex, we reasoned that histone PTMs that promote the interaction of NuA3 with chromatin would colocalize with Sas3. To this end, we mapped NuA3-bound nucleosomes at high resolution in vivo using a MNase-based ChIP-seq approach, which has previously been used to map chromatin remodelers (Koerber et al 2009;Floer et al 2010;Yen et al 2012;Ramachandran et al 2015). We immunoprecipitated HA-tagged Sas3, in parallel with an untagged control, from cross-linked MNase-digested chromatin and performed paired-end sequencing.…”

Section: Nua3 Is Primarily Bound To Midgene Regions Of Actively Transmentioning

confidence: 99%

Histone H3K4 and H3K36 Methylation Independently Recruit the NuA3 Histone Acetyltransferase in Saccharomyces cerevisiae

et al. 2017

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Histone post-translational modifications (PTMs) alter chromatin structure by promoting the interaction of chromatinmodifying complexes with nucleosomes. The majority of chromatin-modifying complexes contain multiple domains that preferentially interact with modified histones, leading to speculation that these domains function in concert to target nucleosomes with distinct combinations of histone PTMs. In Saccharomyces cerevisiae, the NuA3 histone acetyltransferase complex contains three domains, the PHD finger in Yng1, the PWWP domain in Pdp3, and the YEATS domain in Taf14; which in vitro bind to H3K4 methylation, H3K36 methylation, and acetylated and crotonylated H3K9, respectively. While the in vitro binding has been well characterized, the relative in vivo contributions of these histone PTMs in targeting NuA3 is unknown. Here, through genome-wide colocalization and by mutational interrogation, we demonstrate that the PHD finger of Yng1, and the PWWP domain of Pdp3 independently target NuA3 to H3K4 and H3K36 methylated chromatin, respectively. In contrast, we find no evidence to support the YEATS domain of Taf14 functioning in NuA3 recruitment. Collectively our results suggest that the presence of multiple histone PTM binding domains within NuA3, rather than restricting it to nucleosomes containing distinct combinations of histone PTMs, can serve to increase the range of nucleosomes bound by the complex. Interestingly, however, the simple presence of NuA3 is insufficient to ensure acetylation of the associated nucleosomes, suggesting a secondary level of acetylation regulation that does not involve control of HAT-nucleosome interactions.

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Genome-wide Nucleosome Specificity and Directionality of Chromatin Remodelers

Cited by 320 publications

References 67 publications

Multiple modes of regulation of the human Ino80 SNF2 ATPase by subunits of the INO80 chromatin-remodeling complex

Multiple modes of regulation of the human Ino80 SNF2 ATPase by subunits of the INO80 chromatin-remodeling complex

Structural evidence for Nap1‐dependent H2A–H2B deposition and nucleosome assembly

Histone H3K4 and H3K36 Methylation Independently Recruit the NuA3 Histone Acetyltransferase in Saccharomyces cerevisiae

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